The long range goal of this project is to investigate the pathophysiology of hypersensitivity granulomas in the skin as they compare with other types of inflammation including foreign body granulomas. A novel cutaneous model has been developed in the mouse by transplantation of granulomas which develop in the liver of mice infected with Schistosoma mansoni. Specifically, we aim to study how granulomas develop in the skin in a microenvironment of T-cell intact or athymic mice and what factors are responsible for elicitation of the unique type of tissue reaction. Morphological and biochemical changes that occur in the tissue transplant will be examined morphologically (by light and electron microscopy) and functionally (by autoradiographic, cytochemical, biochemical and enzymological techniques). The length of time that cutaneous involvement persists will be determined. Modulation of granulomas in the skin after administration of enzyme and mediator inhibitors will be monitored by the various parameters. The findings will be compared with similar observations and measurements previously made in hypersensitivity granulomas of the liver and in nonimmunologic foreign body granulomas experimentally produced in the skin of mice. The information obtained is expected to improve our understanding of granulomatous diseases and to help develop newer and possibly more beneficial ways to treat and control crippling granulomatous diseases of man.